蜕膜化
间质细胞
胚泡
PTEN公司
生物
子宫内膜
细胞生物学
男科
内分泌学
内科学
癌症研究
胚胎
PI3K/AKT/mTOR通路
医学
信号转导
胚胎发生
作者
Yuan Zhu,B. Zheng,Yuting Zhang,Mengyun Li,Yuan Jiang,Jidong Zhou,Yang Zhang,Nannan Kang,Min Wu,Yan Yuan,Jun Xing,Jianjun Zhou
出处
期刊:Molecular human reproduction
[Oxford University Press]
日期:2024-12-01
卷期号:30 (12)
标识
DOI:10.1093/molehr/gaae042
摘要
Abstract Endometrial collagen I undergoes dynamic degradation and remodelling in response to endometrial stromal cell (ESC) decidualization and embryo implantation. However, excessive collagen I deposition in the endometrium during the implantation window may impair decidualization, causing embryo implantation failure in patients with endometriosis (EMS). We found that endometrial collagen I expression during the mid-secretory phase was increased in the EMS group of patients. Collagen I stimulation resulted in decreased expression of the decidualization markers prolactin and insulin-like growth factor binding protein-1 in ESCs, impeding ESC transformation to a decidual morphology and decreasing the blastocyst-like spheroid expansion area in vitro. Treatment with extracellular vesicles (EVs) derived from the ectopic ESCs of EMS patients (EMS-EVs) increased collagen I expression in vivo and in vitro and decreased the blastocyst-like spheroid expansion area. Furthermore, EV microRNA (miRNA) sequencing revealed that there were 40 upregulated and 77 downregulated miRNAs in EMS-EVs when compared to the EVs derived from ESCs in the endometrium of control patients (CTL-EVs), including increased expression of miR-25-3p that targets phosphatase and tensin homolog (PTEN). We also found that PTEN expression was decreased and p-Akt expression was increased in the endometrium of EMS patients and EMS-EV-treated ESCs. miR-25-3p transfected ESCs exhibited increased collagen I, decreased PTEN, and increased p-Akt. Additionally, an EV uptake study further showed that EMS-EVs were preferentially taken up by ESCs rather than by endometrial epithelial cells. These results suggest that EMS-EVs encapsulating miR-25-3p might be preferentially taken up by eutopic ESCs where they may induce endometrial collagen I deposition to impair ESC decidualization in EMS.
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